I have an itchy, painful, edematous rash that is spreading and involves my lips and eyelids; what condition is most likely?

Severe Drug Reaction with Systemic Involvement: DRESS Syndrome Most Likely

Based on your presentation of an itchy, painful, edematous rash spreading to involve lips and eyelids, you most likely have DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms), a potentially life-threatening drug hypersensitivity reaction that requires immediate medical attention and hospitalization. 1, 2

Why DRESS Syndrome is the Primary Diagnosis

The combination of spreading rash with facial edema (lips and eyelids), pain, and pruritus occurring 2-6 weeks after starting a new medication is pathognomonic for DRESS syndrome. 1, 2 The facial involvement with edema distinguishes this from simple drug rashes and points toward a severe systemic reaction. 3, 2

Key Distinguishing Features Present in Your Case:

• Facial edema involving lips and eyelids - This mucocutaneous involvement with swelling is characteristic of DRESS, not typical drug rashes 2, 4
• Spreading nature - DRESS characteristically involves >30% body surface area with a morbilliform (maculopapular) confluent pattern 1, 2, 4
• Pain and pruritus together - The combination suggests severe inflammation beyond simple allergic reaction 2

Critical Differential Diagnoses to Rule Out

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN)

You must be evaluated emergently to exclude SJS/TEN, which presents with painful mucosal erosions, skin sloughing, and has 25-35% mortality. 5, 6 However, DRESS is more likely because:

• SJS/TEN typically shows skin detachment and blistering, not just edema 5, 7
• SJS/TEN has hemorrhagic erosions of mucous membranes, not just swelling 5
• Your description emphasizes swelling rather than skin peeling 3, 5

Angioedema

Less likely because angioedema typically:

• Involves deeper dermal/submucosal swelling without rash 3
• Does not present with spreading maculopapular eruption 1
• Resolves within 24-72 hours, not progressively spreading 3

Immediate Actions Required

1. Emergency Evaluation (Within Hours)

Go to an emergency department immediately for:

• Complete blood count with differential to check for eosinophilia (>700/μL or >10%) 1, 2, 4
• Comprehensive metabolic panel evaluating liver function (ALT, AST) and kidney function (creatinine, BUN) 1, 2, 4
• Assessment of body surface area involvement 1, 2
• Evaluation for fever >38°C 1, 2, 4
• Urinalysis to evaluate for nephritis 1, 2

2. Drug History is Critical

Identify any medication started 2-6 weeks ago, as this latency period is diagnostic for DRESS. 1, 2, 4 The most common culprits are:

• Anticonvulsants (carbamazepine, phenytoin, phenobarbital) - 21% of cases 2
• Antibiotics (vancomycin, sulfonamides, beta-lactams) - 74% of cases 2
• Allopurinol - strongly associated with HLA-B*58:01 1, 2
• Antiretrovirals (nevirapine 17-32%, abacavir 2.3-9%) 2

3. Immediate Management if DRESS Confirmed

The suspected drug must be stopped immediately - this is the single most important intervention. 1, 2

You will require hospitalization, likely in an ICU or burn unit, with:

• IV methylprednisolone 1-2 mg/kg/day as first-line therapy 1, 2
• Minimum 4-week steroid taper to prevent relapse (occurs in 12% of cases) 2
• Dermatology consultation within hours 1, 2

Supportive care includes:

• High-potency topical corticosteroids (clobetasol 0.05% or betamethasone 0.1%) for skin lesions 2
• Oral antihistamines (loratadine 10 mg daily) for pruritus 2
• For severe oral involvement: viscous lidocaine 2% and dexamethasone 0.1 mg/mL mouth rinse 2

Red Flags Requiring Immediate ICU Admission

Seek emergency care immediately if you develop ANY of the following:

• Skin sloughing or blistering (suggests SJS/TEN progression) 3, 5
• Difficulty breathing or chest pain (cardiac/pulmonary involvement) 2, 4
• Decreased urine output (renal involvement) 2, 4
• Confusion or altered mental status 2
• High fever with rigors 2, 4

Critical Pitfalls to Avoid

Do NOT:

• Wait to see if the rash improves on its own - DRESS has 10% mortality without treatment 6
• Take any antihistamines or steroids before being evaluated, as this may mask diagnostic findings 1
• Ever rechallenge with the suspected drug - this causes severe T-cell-mediated reactions with memory responses 2
• Undergo patch testing or intradermal testing until at least 6 months after complete resolution and 4 weeks after stopping systemic steroids 2

Prognosis and Long-Term Considerations

With prompt recognition and treatment, most patients recover fully, but:

• Relapse occurs in 12% of cases if steroids are tapered too quickly 2
• Mortality is approximately 10% with DRESS, primarily from hepatic failure or cardiac involvement 6, 8
• You will need genetic testing (HLA typing) to identify future drug risks 1, 2
• All first-degree relatives should be informed to avoid the culprit drug 6

The presence of facial edema with spreading rash demands immediate evaluation to differentiate DRESS from life-threatening SJS/TEN - do not delay seeking emergency care. 3, 1, 5